NM_000059.3(BRCA2):c.6275_6276delTT (p.Leu2092Profs) AND Hereditary breast and ovarian cancer syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 17, 2016
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000044884.6

Allele description

NM_000059.3(BRCA2):c.6275_6276delTT (p.Leu2092Profs)

Gene:

BRCA2:BRCA2, DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.3(BRCA2):c.6275_6276delTT (p.Leu2092Profs)

Other names:

6503_6504delTT

HGVS:

NC_000013.11:g.32340630_32340631delTT
NG_012772.3:g.30151_30152delTT
NM_000059.3:c.6275_6276delTT
NP_000050.2:p.Leu2092Profs
LRG_293t1:c.6275_6276delTT
LRG_293:g.30151_30152delTT
LRG_293p1:p.Leu2092Profs
NC_000013.10:g.32914767_32914768delTT
NM_000059.3:c.6275_6276del
U43746.1:n.6503_6504delTT
p.L2092Pfs*7
p.L2092PfsX7
p.Leu2092Profs*7

Nucleotide change:

6503delTT

Links:

Breast Cancer Information Core (BIC) (BRCA2): 6503&base_change=del TT; OMIM: 600185.0002; dbSNP: rs11571658

NCBI 1000 Genomes Browser:

rs11571658

Allele Frequency:

0.00002(-)

Molecular consequence:

NM_000059.3:c.6275_6276delTT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:: Hereditary breast and ovarian cancer
Identifiers:: MedGen: C0677776; Orphanet: 145
Prevalence:: http://www.ncbi.nlm.nih.gov/books/NBK1247/ https://www.ncbi.nlm.nih.gov/books/NBK1247

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000072897	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 17, 2016)	germline	clinical testing	Citation Link,
SCV000324882	Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG guidelines, 2007)	Pathogenic (Jun 29, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000072897

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 17, 2016)

germline

clinical testing

Citation Link,

SCV000324882

Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG guidelines, 2007)

Pathogenic
(Jun 29, 2015)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Details of each submission

From Invitae, SCV000072897.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This sequence change deletes 2 nucleotides from exon 11 of the BRCA2 mRNA (c.6275_6276delTT), causing a frameshift at codon 2092. This creates a premature translational stop signal (p.Leu2092Profs*7) and is expected to result in an absent or disrupted protein product. Truncating variants in BRCA2 are known to be pathogenic. This particular truncation has been reported in patients affected with breast, ovarian, and prostate cancer (PMID: 8524414, 22009639, 21324516, 22006311, 20736950, 23199084). This variant is also known as 6503delTT in the literature. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario, SCV000324882.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Interpretation was last updated within 1 year from 6/29/2015 6:14 PM

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 25, 2017

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